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目的：发展一种根据受体三维结构搜寻配体活性构象的方法．方法：结合系统构象搜寻方法和配体—受体分子对接（Ｄｏｃｋ）方法，我们发展了一种根据受体三维结构搜寻配体小分子活性构象的方法．结果：应用这一方法，我们搜寻出了膦酰肽类凝血酶抑制剂的活性构象，由搜寻结果，我们又用分子力学方法，计算了膦酰肽类抑制剂和凝血酶的结合能．结论：计算结果表明，这些凝血酶抑制剂和凝血酶的结合能与其抑制活性之间有很好的相关性，这说明我们计算方法的可靠性．同时，计算结果能很好地解释膦酰肽类凝血酶抑制剂的作用机理．
OBJECTIVE: To develop a method for searching the active conformation of ligands based on the three-dimensional structure of the receptor. METHODS: In combination with the systematic conformational search method and the Dock-Docking method, we developed a method to search for the active conformation of small ligands based on the three-dimensional structure of the acceptor. Results: Using this method, we searched out the active conformation of the phosphonopeptide thrombin inhibitor. From the search results, we calculated the binding energy of the phosphonopeptide inhibitor and thrombin using molecular mechanics. CONCLUSIONS: The calculated results show that there is a good correlation between the binding energy of these thrombin inhibitors and thrombin and their inhibitory activity, which shows the reliability of our method. At the same time, the calculation results can well explain the mechanism of action of phosphonopeptide thrombin inhibitors.